Binding of carcinogenic polycyclic aromatic hydrocarbons (PAH) to a cellular macromolecular target is hypothesized to be the first step in the tumorigenesis process. The research proposed here consists of comparing the binding of selected carcinogenic PAH to nucleic acids in several in vitro and in vivo systems. Binding of (14C) 6-methylbenzo(a)pyrene (BP-6-CH3) to DNA in nuclei isolated from Sprague-Dawley rat livers and to DNA and RNA in the skin of Swiss mice will be compared with that bound to calf thymus DNA by purified horseradish peroxidase, a possible model system for activation by one-electron oxidation. The adducts will be degraded to monomeric units enzymatically and chemically, and analyzed by chromatography on Sephadex LH2O and by high pressure liquid chromatography. Similarly the binding of (14C)7-methylbenz(a)anthracene (BA-7-CH3) to skin nucleic acids will be analyzed and compared to the binding of the sulfate ester of (14C)BA-7-CH2OH (BA-7-CH2OSO3) to calf thymus DNA. Binding of BP-6-CH3 by peroxidase is expected to yield sufficient amounts of hydrocarbon-nucleic acid base or nucleoside adducts for chemical analysis. Use of the BA-7-CH2OSO3 also will enable chemical analysis and possibly identification of adducts. The structure of adducts from binding in nuclei or skin which co-chromatograph with the adducts will then be identified. Preliminary studies will be conducted of binding of three mammary carcinogens to mammary nuclear DNA. The amount of binding will be measured of BP, 7,12-dimethyl-benz(a)anthracene and 3-methylcholanthrene to DNA in isolated nuclei from 50- to 60- day-old virgin Sprague-Dawley rats. These studies will provide information necessary to study in more depth the biochemistry of PAH activation in the mammary gland.